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EFEK EKSTRAK DAUN TANJUNG (Mimusops elengi Linn.)
TERHADAP GAMBARAN HISTOPATOLOGI LAMBUNG
TIKUS PUTIH JANTAN GALUR WISTAR YANG DIINDUKSI
ASPIRIN
SKRIPSI
PUTRI ANGGRAENI KUSUMAWARDHANI
1210211019
UNIVERSITAS PEMBANGUNAN NASIONAL “VETERAN”JAKARTA
FAKULTAS KEDOKTERAN
PROGRAM STUDI SARJANA KEDOKTERAN
2016
EFEK EKSTRAK DAUN TANJUNG (Mimusops elengi Linn.)
TERHADAP GAMBARAN HISTOPATOLOGI LAMBUNG
TIKUS PUTIH JANTAN GALUR WISTAR YANG DIINDUKSI
ASPIRIN
SKRIPSI
Diajukan Sebagai Salah Satu Syarat Untuk Memperoleh Gelar
Sarjana Kedokteran
PUTRI ANGGRAENI KUSUMAWARDHANI
121.0211.019
UNIVERSITAS PEMBANGUNAN NASIONAL “VETERAN”JAKARTA
FAKULTAS KEDOKTERAN
PROGRAM STUDI SARJANA KEDOKTERAN
2016
v
EFEK EKSTRAK DAUN TANJUNG (MIMUSOPS ELENGI
LINN.) TERHADAP GAMBARAN HISTOPATOLOGI
LAMBUNG TIKUS PUTIH JANTAN GALUR WISTAR YANG
DIINDUKSI ASPIRIN
Putri Anggraeni Kusumawardhani
Abstrak
NSAID adalah obat yang termasuk salah satu faktor agresif, sehingga dalam
pemakaian jangka waktu lama menyebabkan inflamasi mukosa lambung,
pengikisan dan ulserasi mukosa saluran cerna atas. Aspirin sebagai obat golongan
NSAID banyak digunakan sebagai anti inflamasi dan pengobatan serebrovaskular.
Untuk melindungi lambung dari efek aspirin maka dapat menggunakan alternatif
ekstrak daun tanjung (Mimusops elengi Linn.). Penelitian ini adalah penelitian
eksperimental laboratorium dengan desain post test only group. Hewan uji yang
digunakan adalah tikus jantan galur wistar berjumlah 30 ekor dan dibagi menjadi
6 kelompok. Kelompok terdiri dari kelompok 1 sebagai kontrol (CMC), kelompok
2 dengan pemberian aspirin dosis 90 mg/ekor, kelompok 3, kelompok 4 dan
kelompok 5 diberikan ekstrak daun tanjung dosis 100 mg/kgBB, 200 mg/kgBB,
400 mg/kgBB dan ditambah aspirin 90 mg/ekor serta kelompok 6 sebagai kontrol
positif (misoprostol 3,6 μg/ekor). Preparat histologi tikus dilihat dengan
mikroskop pembesaran 100x dan 400x dan dinilai berdasarkan skor ringan,
kerusakan sedang dan kerusakan berat. Data dianalisis dengan uji Kruskal-Wallis
dan uji Mann-Whitney. Hasil significant value uji Kruskal-Wallis adalah 0,000
(P<0,005) yang membuktikan bahwa terdapat perbedaan antara dua kelompok.
Hasil uji Mann-Whitney menunjukkan antara kelompok yang diberikan aspirin
dengan masing-masing kelompok dan antara kelompok kontrol negatif dengan
kelompok perlakuan ekstrak 100 mg/kgBB memiliki perbedaan yang bermakna.
Antara kelompok kontrol negatif dengan kelompok perlakuan ekstrak 400
mg/kgBB, kontrol positif dan masing-masing kelompok yang diberikan ekstrak
daun tanjung memiliki perbedaan yang tidak bermakna. Ekstrak daun tanjung
(Mimusops elengi Linn.) dapat mencegah kerusakan mukosa lambung tikus yang
diinduksi aspirin dengan dosis optimal 400 mg/kgBB.
Kata kunci: Mimusops elengi Linn., aspirin, histopatologi, lambung
vi
THE EFFECT OF TANJUNG LEAF EXTRACT (MIMUSOPS
ELENGI LINN.) TO WHITE WISTAR MALE RAT’S GASTRIC
HISTOPATHOLOGY INDUCED ASPIRIN
Putri Anggraeni Kusumawardhani
Abstract
NSAIDs are drugs that included one of the factors resulting in the aggressive use
of long periods of time may cause inflammation of the gastric mucosa, erosion
and ulceration of the mucosa of the upper gastrointestinal tract. The most widely
used NSAID is aspirin. Aside from being an anti-inflammatory aspirin is widely
used as a treatment of cerebrovascular. To protect the stomach from the effects of
aspirin, it can use alternate Tanjung leaf extract (Mimusops elengi Linn.). This
study is an experimental research laboratory with post test only group. Test
animals used were male rats wistar strain amounted to 30 individuals, and divided
into 6 groups. The Group consists of a group 1 as control (CMC), group 2 with
aspirin doses of 90 mg / tail, the group 3, group 4, group 5 with Tanjung leaf
extract dose of 100 mg / kg, 200 mg / kg, 400 mg / kg and aspirin 90 mg / tail,
group 6 as the positive control group (misoprostol 3.6 mg / head). Histological
preparations of mice under the microscope magnification of 100x and 400x and
evaluated according to mild, moderate damage and severe damage. Data were
analyzed with the Kruskal-Wallis and Mann-Whitney test.
The results of significant value Kruskal-Wallis test was 0.000 (P <0.005), which
proves that there is a difference between the two groups. Mann-Whitney test
results showed the group given aspirin with each group and between groups of
negative control with group treated the extract 100 mg /kg and 200mg/kg had a
significant difference. While the negative control group treated with the extract
400 mg / kg, positive control and each group was given the Tanjung leaf extract
had not a significant difference. Tanjung leaf extract (Mimusops elengi Linn.) can
prevent gastric mucosal damage induced mice aspirin. Optimal dose of Tanjung
leaf extract (Mimusops elengi Linn.) is 400 mg/kg.
Keywords: Mimusops elengi Linn., aspirin, histopathology, gastric
vii
KATA PENGANTAR
Puji dan syukur penulis panjatkan atas kehadirat Allah SWT atas segala
karunia-Nya sehingga skripsi ini berhasil diselesaikan. Judul yang dipilih dalam
penelitian ini yang dilaksanakan sejak Bulan Februari tahun 2016 ini adalah Efek
Ekstrak Daun Tanjung (Mimusops elengi Linn.) Terhadap Gambaran
Histopatologi Lambung Tikus Putih Jantan Galur Wistar yang Diinduksi Aspirin.
Terima kasih penulis ucapkan kepada Ibu Sri Rahayu, Ssi, Msi, Apt dan Ibu dra.
Cut Fauziah, M.Biomed selaku dosen pembimbing yang telah banyak
memberikan saran yang sangat bermanfaat.
Disamping itu, ucapan terima kasih juga disampaikan kepada Bapak,
Angger Waspodo, S.H, M.H dan Ibu, drg. Rr. Elista Soekmawardhani, M.Kes
serta seluruh keluarga yang tidak henti-hentinya memberikan penulis semangat
dan doa. Penulis juga sampaikan terima kasih kepada teman-teman yang telah
membantu dalam penulisan skripsi ini.
Jakarta, 3 Mei 2016
Penulis
Putri Anggraeni Kusumawardhani
ix
DAFTAR ISI
HALAMAN JUDUL ................................................................................ i
PERNYATAAN ORISINALITAS............................................................. ii
PERNYATAAN PERSETUJUAN PUBLIKASI ...................................... iii
PENGESAHAN ......................................................................................... iv
ABSTRAK ................................................................................................. v
ABSTRACT ................................................................................................. vi
KATA PENGANTAR ............................................................................... vii
DAFTAR ISI ............................................................................................. viii
DAFTAR TABEL ...................................................................................... xi
DAFTAR GAMBAR ................................................................................. x
DAFTAR LAMPIRAN .............................................................................. xi
BAB I PENDAHULUAN .......................................................................... 1
I.1 Latar Belakang ...................................................................................... 1
I.2 Rumusan Masalah ................................................................................. 3
I.3 Tujuan Penelitian .................................................................................. 3
I.4 Manfaat Penelitian ................................................................................ 3
BAB II TINJAUAN PUSTAKA ................................................................ 5
II.1 Landasan Teori ..................................................................................... 5
II.1.1 Lambung ............................................................................................ 5
II.1.1.1 Anatomi Lambung .......................................................................... 5
II.1.1.2 Histologi Lambung ......................................................................... 7
II.1.1.3 Fisiologi Lambung .......................................................................... 10
II.1.1.3.1 Perlindungan Mukosa Lambung .................................................. 10
II.1.1.3.2 Proses Sekresi Lambung .............................................................. 11
II.1.1.3.3 Sintesis Asam Hidroklorida (HCl) .............................................. 12
II.1.2 Gangguan yang Terjadi Pada Lambung ............................................ 13
II.1.2.1 Gastritis .......................................................................................... 13
II.1.2.1.1 Klasifikasi Gastritis ..................................................................... 13
II.1.2.2 Ulkus Lambung .............................................................................. 15
II.1.2.2.1 Penyebab ..................................................................................... 16
II.1.2.2.2 Patofisiologi ................................................................................. 17
II.1.2.2.3 Gejala Klinis ................................................................................. 18
II.1.2.2.4 Pemeriksaan Penunjang ................................................................ 18
II.1.2.2.5 Tata Laksana Ulkus Lambung ...................................................... 19
II.1.3 Aspirin ................................................................................................ 27
II.1.3.1 Farmakokinetik ................................................................................ 28
II.1.3.2 Farmakodinamik .............................................................................. 28
II.1.3.3 Efek Samping .................................................................................. 29
II.1.3.4 Interaksi Obat .................................................................................. 29
II.1.4 Hubungan Antara NSAID Dengan Ulkus Lambung ......................... 29
II.1.5 Hewan Coba ....................................................................................... 30
x
II.1.6 Pohon Tanjung ................................................................................... 33
II.1.6.1 Morfologi Pohon Tanjung ............................................................... 33
II.1.6.2 Manfaat Pohon Tanjung .................................................................. 34
II.1.6.3 Kandungan Kimia ........................................................................... 35
II.1.7 Ekstraksi ............................................................................................. 38
II.1.7.1 Faktor Penentu Ekstrak ................................................................... 38
II.1.7.2 Metode Ekstraksi Cara Dingin ................................. ....................... 38
II.1.7.3 Metode Ekstraksi Cara Panas .......................................................... 39
II.2 Kerangka Teori ...................................................................................... 40
II.3 Kerangka Konsep .................................................................................. 41
II.4 Hipotesis ................................................................................................ 41
BAB III METODOLOGI PENELITIAN .................................................. 42
III.1 Jenis Penelitian .................................................................................... 42
III.2 Waktu dan Tempat Penelitian ............................................................. 42
III.3 Subjek Penelitian ................................................................................. 42
III.3.1 Populasi ............................................................................................ 42
III.3.2 Sampel .............................................................................................. 42
III.3.3 Besar Sampel .................................................................................... 43
III.4 Identifikasi Variabel Penelitian ........................................................... 44
III.4.1 Variabel Independen ........................................................................ 44
III.4.2 Variabel Dependen ........................................................................... 44
III.5 Definisi Operasional Variabel .............................................................. 44
III.6 Instrumen Penelitian ............................................................................ 47
III.6.1 Bahan Penelitian ............................................................................... 47
III.6.2 Alat Penelitian .................................................................................. 48
III.7 Protokol Penelitian .............................................................................. 48
III.7.1 Persiapan Alat dan Bahan Penelitian ............................................... 48
III.7.1.1 Pembuatan Larutan CMC ............................................................. 48
III.7.1.2 Pembuatan Larutan Aspirin .......................................................... 49
III.7.1.3 Pembuatan Larutan Ekstrak Daun Tanjung .................................. 49
III.7.1.4 Pembuatan Larutan Misoprostol ................................................... 50
III.7.2 Perlakuan .......................................................................................... 50
III.7.3 Pembuatan Sediaan Preparat ............................................................ 51
III.7.4 Pengamatan Jaringan ........................................................................ 53
III.8 Alur Penelitian ..................................................................................... 55
III.9 Analisis Data ....................................................................................... 56
BAB IV HASIL DAN PEMBAHASAN ................................................... 57
IV.1 Hasil Penelitian .................................................................................... 57
IV.2 Analisis Data ....................................................................................... 58
IV.2.1 Uji Normalitas .................................................................................. 58
IV.2.2 Uji Varians ....................................................................................... 59
IV.2.3 Uji Kruskall-Wallis .......................................................................... 60
IV.2.4 Uji Mann-Whitney ........................................................................... 61
IV.3 Pembahasan ......................................................................................... 62
IV.3.1 Prosedur Penelitian ........................................................................... 62
IV.3.1.1 Pemilihan Metode .......................................................................... 62
xi
IV.3.1.2 Pemilihan Bahan Penelitian .......................................................... 63
IV.3.1.3 Pemilihan Sampel ......................................................................... 65
IV.3.2 Hasil Uji ........................................................................................... 65
IV.3.2.1 Kelompok Kontrol Negatif ........................................................... 65
IV.3.2.2 Kelompok Pemberian Aspirin 90 mg/ekor .................................... 66
IV.3.2.3 Kelompok Ekstrak Daun Tanjung ................................................. 68
IV.3.2.4 Kelompok Kontrol Positif ............................................................. 71
BAB V PENUTUP ..................................................................................... 72
V.1 Kesimpulan ........................................................................................... 72
V.2 Saran ..................................................................................................... 72
DAFTAR PUSTAKA ................................................................................. 73
RIWAYAT HIDUP
LAMPIRAN
xii
DAFTAR TABEL
Tabel 1 Klasifikasi Gastritis Menurut Sidney System........................ 14
Tabel 2 Penyebab Ulkus Lambung Selain Helicobacter pylori
dan NSAID .......................................................................... 16
Tabel 3 Perbedaan Ulkus Lambung Jinak dengan Ulkus
Lambung Ganas ................................................................... 19
Tabel 4 Sifat Biologis dan Fisiologis Tikus
Putih (Rattus norvegicus) .................................................... 31
Tabel 5 Definisi Operasional ............................................................ 44
Tabel 6 Derajat Gambaran Histopatologi Lambung ......................... 53
Tabel 7 Hasil Efek Ekstrak Daun Tanjung Terhadap
Gambaran Histopatologi Lambung Tikus ........................... 57
Tabel 8 Hasil Uji Normalitas ............................................................ 59
Tabel 9 Hasil Uji Varians ................................................................. 60
Tabel 10 Hasil Uji Kruskal-Wallis ..................................................... 60
Tabel 11 Ringkasan Hasil Uji Mann-Whitney Terhadap
Kelompok Perlakuan ........................................................... 61
xiii
DAFTAR GAMBAR
Gambar 1 Anatomi Lambung ............................................................... 6
Gambar 2 Vaskularisasi Arteri Lambung ............................................. 7
Gambar 3 Tunika Mukosa Lambung .................................................... 9
Gambar 4 Lapisan Pertahanan Mukosa ................................................ 10
Gambar 5 Mekanisme Sintesis Prostaglandin ...................................... 11
Gambar 6 Mekanisme Sekresi HCl ...................................................... 13
Gambar 7 Struktur Molekul Aspirin .................................................... 27
Gambar 8 Pohon Tanjung (Mimusops elengi Linn.) ............................ 33
Gambar 9 Kulit Batang, Daun dan Buah Pohon Tanjung .................. 34
Gambar 10 Struktur Dasar Sapponin ...................................................... 36
Gambar 11 Struktur Dasar Tannin .......................................................... 37
Gambar 12 Struktur Dasar (a) Tripertenoid (b) Steroid ......................... 37
Gambar 13 Kerangka Teori .................................................................... 40
Gambar 14 Kerangka Konsep ................................................................ 41
Gambar 15 Alur Penelitian ..................................................................... 55
xiv
DAFTAR LAMPIRAN
Lampiran 1 Surat Izin Penelitian Kepada Kepala BALITTRO
Lampiran 2 Surat Izin Penelitian Kepada Kepala Departemen Farmakologi
FKUI
Lampiran 3 Surat Izin Penelitian Kepada Kepala Departemen Patologi Anatomi
FK UPN “Veteran” Jakarta
Lampiran 4 Surat Izin Penelitian Kepada Kepala Departemen Patologi Anatomi
FK UI
Lampiran 5 Surat Konfirmasi Kepala Departemen Patologi Anatomi FK UI
Lampiran 6 Surat Izin Penelitian Kepada Kepala Badan Litbang Kesehatan
Puslitbang Pemberantasan Penyakit Lab. Hewan Percobaan dan
Toksikologi
Lampiran 7 Ethical Clearence Komisi Etik Penelitian FK UPN “Veteran”
Jakarta
Lampiran 8 Sertifikat Hasil Uji Fitokimia Ekstrak Daun Tanjung
Lampiran 9 Surat Izin Kepada Manajer Laboratorium UI-Olympus Bioimaging
Center
Lampiran 10 Letter of Support Laboratorium UI-Olympus Bioimaging Center
Lampiran 11 Perhitungan Dosis Aspirin
Lampiran 12 Perhitungan Dosis Misoprostol
Lampiran 13 Tabel Konversi Perhitungan Dosis (Laurence & Bacharach, 1964)
Lampiran 14 Foto Hasil Pra Eksperimen
Lampiran 15 Foto Alat Pembuatan Ekstrak Daun Tanjung
Lampiran 16 Foto Persiapan Pemberian Obat dan Ekstrak
Lampiran 17 Foto Kelompok Sampel
Lampiran 18 Foto Keadaan Kandang dan Perlakuan
Lampiran 19 Foto Anastesi dan Pembedahan Tikus
Lampiran 20 Foto Laboratorium Pembuatan Slide Histopatologi
Lampiran 21 Foto Gambaran Histopatologi Lambung Tikus yang Diinduksi
Aspirin
Lampiran 22 Tabel Hasil Uji SPSS